The male-specific region of the Y chromosome, the MSY, differentiates the sexes and comprises 95% of the chromosome's length. Here, we report that the MSY is a mosaic of heterochromatic sequences and three classes of euchromatic sequences: X-transposed, X-degenerate and ampliconic. These classes contain all 156 known transcription units, which include 78 protein-coding genes that collectively encode 27 distinct proteins. The X-transposed sequences exhibit 99% identity to the X chromosome. The X-degenerate sequences are remnants of ancient autosomes from which the modern X and Y chromosomes evolved. The ampliconic class includes large regions (about 30% of the MSY euchromatin) where sequence pairs show greater than 99.9% identity, which is maintained by frequent gene conversion (non-reciprocal transfer). The most prominent features here are eight massive palindromes, at least six of which contain testis genes.

this diversity is located in discrete gene clusters that are spread throughout the different genomes. In contrast to this diversity, these enteric microorganisms exhibit marked synteny in their largescale genomic organization, bearing in mind that E. coli and S. enterica diverged about 100 Myr ago 28. The conserved genes may be a re¯ection of the basic lifestyle of the bacteria, requiring intestine colonization, environmental survival and transmission. The unique gene clusters probably contribute to adaptation to environmental niches and to pathogenicity. The pseudogene complement of S. typhi has implications for our understanding of the tight host restriction of this organism, and raises the question of whether it may be possible to eradicate S. typhi and typhoid fever altogether. M Methods Salmonella typhi CT18 was isolated in December 1993, at the Mekong Delta region of Vietnam, from a 9-year-old girl who was suffering from typhoid. The strain was isolated from blood using routine culture methods 23 , and after serological and metabolic con-®rmation of the strain as S. typhi it was immediately frozen in glycerol at-70 8C. The genome sequence was obtained from 97,000 end sequences (giving 7.9´coverage) derived from several pUC18 genomic shotgun libraries (with insert sizes ranging from 1.4 to 4.0 kb) using dye terminator chemistry on ABI377 automated sequencers. This was supplemented with 0.7´sequence coverage from M13mp18 libraries with similar insert sizes. End sequences from a larger insert plasmid (pSP64; 1.9´clone coverage, 10±14-kb insert size) and lambda (lambda-FIX-II; 0.4´clone coverage, 20±22-kb insert size) libraries were used as a scaffold, and the ®nal assembly was veri®ed by comparison with restriction-enzyme digest patterns using pulsed-®eld gel electrophoresis (data not shown). Total sequence coverage was 9.1´. The sequence was assembled, ®nished and annotated as described 29 , using Artemis 30 to collate data and facilitate annotation. In addition we used a gene®nder that was trained speci®cally for S. typhi, which uses a hidden Markov model with modules for the coding region, start and stop codons, and the ribosome-binding site (T.S.L. and A.K., unpublished data). The genome and proteome sequences of S. typhi and S. typhimurium or E. coli were compared in parallel to identify deletions and insertions using the Artemis Comparison Tool (ACT) (K. Rutherford, unpublished data; see also http://www.sanger.ac.uk/Software/ ACT/). Pseudogenes had one or more mutations that would ablate expression, and were identi®ed by direct comparison with S. typhimurium; each of the inactivating mutations was subsequently checked against the original sequencing data.

More detailed sequence standards that keep up with revolutionary sequencing technologies will aid the research community in evaluating data.

The higher plant Arabidopsis thaliana (Arabidopsis) is an important model for identifying plant genes and determining their function. To assist biological investigations and to define chromosome structure, a coordinated effort to sequence the Arabidopsis genome was initiated in late 1996. Here we report one of the first milestones of this project, the sequence of chromosome 4. Analysis of 17.38 megabases of unique sequence, representing about 17% of the genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements. Heterochromatic regions surrounding the putative centromere, which has not yet been completely sequenced, are characterized by an increased frequency of a variety of repeats, new repeats, reduced recombination, lowered gene density and lowered gene expression. Roughly 60% of the predicted protein-coding genes have been functionally characterized on the basis of their homology to known genes. Many genes encode predicted proteins that are homologous to human and Caenorhabditis elegans proteins.

Human chromosome 7 has historically received prominent attention in the human genetics community, primarily related to the search for the cystic fibrosis gene and the frequent cytogenetic changes associated with various forms of cancer. Here we present more than 153 million base pairs representing 99.4% of the euchromatic sequence of chromosome 7, the first metacentric chromosome completed so far. The sequence has excellent concordance with previously established physical and genetic maps, and it exhibits an unusual amount of segmentally duplicated sequence (8.2%), with marked differences between the two arms. Our initial analyses have identified 1,150 protein-coding genes, 605 of which have been confirmed by complementary DNA sequences, and an additional 941 pseudogenes. Of genes confirmed by transcript sequences, some are polymorphic for mutations that disrupt the reading frame.